Marzac C.,University Pierre and Marie Curie |
Marzac C.,Laboratoire dImmunologie et Hematologie Biologique |
Garrido E.,CNRS Natural Product Chemistry Institute |
Tang R.,University Pierre and Marie Curie |
And 9 more authors.
Haematologica | Year: 2011
Background: A major issue in the treatment of acute myeloid leukemia is resistance to chemotherapeutic drugs. An increasing number of ATP-Binding-Cassette transporters have been demonstrated to cause resistance to cancer drugs. The aim of this study was to highlight the putative role of other ATP-Binding-Cassette transporters in primary chemoresistant acute myeloid leukemia. Design and Methods: In the first part of this study, using taqman custom arrays, we analyzed the relative expression levels of 49 ATP-Binding-Cassette genes in 51 patients divided into two extreme cohorts, one very sensitive and one very resistant to chemotherapy. In the second part of this study, we evaluated the prognostic impact, in a cohort of 281 patients, of ATP-Binding-Cassette genes selected in the first part of the study. Results: In the first part of the study, six genes (ATP-Binding-CassetteA2, ATP-Binding-CassetteB1, ATPBinding-CassetteB6, ATP-Binding-CassettC13, ATP-Binding-CassetteG1, and ATP-Binding-CassetteG2) were significantly over-expressed in the resistant group compared with the sensitive group. In the second cohort, overexpression of 5 of these 6 ATP-Binding-Cassette genes was correlated with outcome in univariate analysis, and only the well-known ATP-Binding-CassetteB1 and G2, and the new ATP-Binding-CassetteG1 in multivariate analysis. Prognosis decreased remarkably with the number of these over-expressed ABC genes. Complete remission was achieved in 71%, 59%, 54%, and 0%, (P=0.0011) and resistance disease in 21%, 37%, 43%, and 100% (P<0.0001) of patients over-expressing 0, 1, 2, or 3, ABC genes, respectively. The number of ATP-Binding-Cassette genes expressed, among ATP-Binding-CassetteB1, G1, and G2, was the strongest prognostic factor correlated, in multivariate analysis, with achievement of complete remission (P=0.01), resistant disease (P=0.01), and overall survival (P=0.02). Conclusions: Using expression profiling, we have emphasized the diversity of ATP-Binding-Cassette transporters that cooperate to promote chemoresistance rather than overexpression of single transporters and the putative role of new ATP-Binding-Cassette tranporters, such as ATP-Binding-CassetteG1. Modulation of these multiple transporters might be required to eradicate leukemic cells. ©2011 Ferrata Storti Foundation.
PubMed | Policlinico Umberto
Type: Comparative Study | Journal: International angiology : a journal of the International Union of Angiology | Year: 2012
Ischemic stroke represents a major health problem and it is an important cause of long-term disability. The aim of this study was to compare short-term and mid-term results of carotid endarterectomy and stenting.During a three-year period, we enrolled 300 patients with carotid stenosis that fit with Stroke Prevention and Educational Awareness Diffusion (SPREAD) guidelines and we performed 150 carotid endarterectomy operations (CEA) and 150 carotid artery stenting procedures (CAS) with distal protection devices. All patients underwent preoperative and postoperative: neurological examination, ultrasound imaging, magnetic resonance imaging (MRI) and cognitive tests; moreover all patients were submitted to preoperative, intraoperative and postoperative Transcranial Doppler (TCD) monitoring, in order to detect microembolic signals (MES).Mortality was zero; two patients developed myocardial infarction in the CEA group during follow-up. The main post-operative results after endarterectomy versus CAS were respectively: neurological deficit: 1.3% vs. 3.3%, embolic lesions at postoperative MRI: 4% vs. 34% and worsening of cognitive tests: 4% vs. 25.3%.CEA seems to be the treatment of choice for carotid stenosis, due to its low rate of mortality and morbidity, especially in asymptomatic patients; CAS should be carried out only in particular subgroup of cases, such as: restenosis, previous neck surgery or radian therapy, anatomical high bifurcation or extended lesions. Ongoing multicenter randomized trials may give a definitive answer to this matter.